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Biomedical subjects

M A Jones

Publications and source records attributed to M A Jones.

At least 73 records · Page 4Linked to original sources
PubMed1996

Occurrence of rheumatoid arthritis is not increased in the first degree relatives of a population based inception cohort of inflammatory polyarthritis.

OBJECTIVE: To determine the risk of rheumatoid arthritis (RA) in first degree relatives of a true population based sample of probands with inflammatory polyarthritis. METHODS: In a case-control study, a two stage screening procedure was used to ascertain the prevalence of RA in 518 first degree relatives of 207 Norfolk Arthritis Register cases registered in 1990 and 414 first degree relatives of 180 local controls. An initial joint symptom and medical history questionnaire was followed by a physical examination, and serological and radiological evaluation of those with symptoms. RESULTS: The prevalence of RA in the first degree relatives of all the Norfolk Arthritis Register cases was 7.7/1000, compared with 4.8/1000 in the first degree relatives of the controls, with a risk ratio of 1.6 (95% confidence interval 0.3 to 8.7). This very modest increase was also seen when the analysis was restricted to the first degree relatives of Norfolk Arthritis Register cases who satisfied the American Rheumatism Association criteria for RA: prevalence rate 7.2/1000. CONCLUSION: There was no evidence of an important increased familial risk of RA in this community based sample. These data are compatible with others from immunogenetic studies showing only weak HLA associations with community ascertained RA.

Adolescent↗
PubMed1996

Haemodynamic changes measured by transthoracic bioimpedance during treatment with recombinant human erythropoietin.

Hypertension complicates the treatment of anaemia of chronic renal failure with recombinant human erythropoietin (EPO) in some patients. We conducted a prospective study measuring changes in cardiac index (CI) and systemic vascular resistance index (SVRI) in 29 patients from before commencement of EPO to attainment of target haemoglobin concentration. We used the operator-independent technique of trans-thoracic bioimpedance. The group of patients who developed EPO-induced hypertension (EpHT) were separately analysed and compared with the group who had no change in blood pressure (NC). Our results showed there was a significant rise in SVRI after treatment in EpHT group patients but in the NC group there was a small fall. CI increased significantly in the NC group after treatment but no change was recorded in the EpHT group. These findings clearly demonstrate how the cardiovascular changes differ in patients who develop EPO-induced hypertension.

Adult↗
PubMed1996

Sympathetic stimulation of corneal epithelial proliferation in wounded and nonwounded rat eyes.

PURPOSE: To determine the effect of ocular sympathetic nerves on corneal epithelial proliferation in the rat. METHODS: Osmotic pumps filled with bromodeoxyuridine (BrdU) were implanted subcutaneously in adult rats to label corneal epithelial cells entering the S-phase of the cell cycle during a 24-hour period. Corneas in some animals were wounded with n-heptanol. Several days or weeks before pump implantation, animals were subjected to either unilateral superior cervical ganglionectomy (SCGectomy), unilateral transection of the cervical sympathetic trunk (sympathetic decentralization), bilateral SCGectomy plus unilateral topical norepinephrine administration, or unilateral SCGectomy plus systemic capsaicin administration. Differences in BrdU-labeling indices between experimental and control eyes in each group were determined from cell counts on paraffin sections. RESULTS: Superior cervical ganglionectomy and sympathetic decentralization significantly decreased epithelial proliferation in nonwounded and wounded corneas. Topical applications of norepinephrine to eyes that had been deprived of their sympathetic innervation completely reversed the antiproliferative effect of ocular sympathectomy. Systemic administration of the neurotoxin capsaicin, in conjunction with unilateral SCGectomy, did not alter the proliferative rate; comparison was made to animals that received unilateral SCGectomy only. CONCLUSIONS: Ocular sympathetic nerves stimulate rat corneal epithelial proliferation under normal physiological conditions and during corneal wound healing. The promotion of DNA synthesis by these nerves occurs independently of functional interactions with capsaicin-sensitive, ocular sensory nerves and appears to be related, at least in part, to the release of norepinephrine.

Alcohols↗
PubMed1995

Malignant mixed müllerian tumors of the ovary: experience with surgical cytoreduction and combination chemotherapy.

BACKGROUND: The role of surgical cytoreduction and combination chemotherapy for malignant mixed müllerian tumors (MMMT) of the ovary was evaluated. METHODS: A retrospective review of 27 women with ovarian MMMT treated from 1980 to 1990 was performed. RESULTS: The International Federation of Gynecology and Obstetrics stages for the 27 women were 1 Stage I, 3 Stage II, 17 Stage III, and 6 Stage IV. Only 10 of the 23 patients with Stage III or IV disease were cytoreduced optimally. With respect to postoperative therapy, 3 women received no treatment, 6 were treated with whole abdomen radiotherapy, 1 received melphalan, and 17 received chemotherapy incorporating a platinum agent (3), doxorubicin (4), or both (10). The significant prognostic factors were stage (P < 0.001) and, for women with Stage III or IV disease, the feasibility of cytoreductive surgery (P = 0.03). The four patients in Stages I or II remained disease free after an interval of at least 5 years. The median and 5-year survival rates for patients with Stages III or IV disease was 18 months and 8%, respectively. Patients in Stage III or IV for whom optimal cytoreduction was not possible had a 2-year survival of 14%, whereas optimal cytoreduction was associated with a 52% 2-year survival. Median survival for the 14 women with Stage III or IV ovarian MMMT treated with combination chemotherapy was 25 months and nine women achieved progression free intervals of greater than 18 months. CONCLUSIONS: Aggressive surgical cytoreduction followed by combination chemotherapy may result in improved progression free intervals for women with advanced ovarian MMMT. However, a major improvement in prognosis for this rare malignancy has not yet been achieved.

Aged↗
PubMed1995

Elective ventilation of potential organ donors.

Elective ventilation describes the procedure of transferring selected patients dying from rapidly progressive intracranial haemorrhage from general medical wards to intensive care units for a brief period of ventilation before confirmation of brain stem death and harvesting of organs. This approach in Exeter has led to a rate of kidney retrieval and transplant higher than has been achieved elsewhere in the United Kingdom, with a stabilisation of numbers on patients on dialysis. Recently doubt has been cast on the legality of our practice of elective ventilation on the grounds that relatives are not permitted to consent to treatment of an incompetent person when that treatment is not in the patient's best interests. We are thus faced with the dilemma of a protocol that is ethical, practical, and operates for the greater good but which may be illegal. This article explores various objections to the protocol and calls for public, medical, and legal debate on the issues.

Brain Death↗
PubMed1995

Induction of interleukin-2 transcription by the hamster polyomavirus middle T antigen: a role for Fyn in T cell signal transduction.

The transforming protein of mouse polyomavirus, the mouse middle T antigen (MomT), and its counterpart in the hamster polyomavirus, the hamster middle T antigen (HamT), interact with a number of cellular proteins. Among these are members of the Src family of tyrosine kinases, the phosphatidylinositol 3-kinase, the serine/threonine phosphatase PP2A and the adaptor protein Shc (in the case of MomT). However, both the relative affinity of these antigens for the members of the Src family and the tumor profile induced by their respective viruses are quite distinct. Particularly noteworthy are the preferential binding of Fyn by HamT and the induction of lymphoid malignancies by the hamster polyomavirus. Here we report that, when expressed in fibroblasts, HamT also associated with phospholipase C gamma (PLC gamma), which led to an increased intracellular concentration of inositol-1, 4, 5-trisphosphate. We also show that expression of HamT in the mouse T cell line EL4 was sufficient to induce transcription from interleukin-2 (IL-2), NFAT and NF kappa B reporter constructs. The immunosuppressant FK506 as well as dominant negative alleles of Ras and Raf inhibited HamT-induced IL-2 transcription. This, together with the observation of NFAT responses, suggests that the action of HamT depended at least in part on the integrity of signal transduction pathways elicited by activated PLC gamma. Furthermore, dominant negative Fyn but not the equivalent allele of Lck blocked HamT activation of IL-2 transcription, while both Lck and Fyn dominant negative alleles blocked LT cell receptor-mediated IL-2 transcriptional activation. These results support the hypothesis that Fyn is involved in signal transduction events leading to IL-2 transcriptional activation in T cells. Finally, the activation of IL-2 transcription by HamT and not by MomT shown here parallels the ability of the hamster polyomavirus to induce lymphoid malignancies.

3T3 Cells↗
PubMed1995

Primary osseous malignant fibrous histiocytoma involving a rib.

A case is presented of an 86-year-old man who developed progressive chest wall pain over a 16-month period. Radiologic studies demonstrated lytic destruction of the right fourth rib anterolaterally. A limited thoracotomy led to the diagnosis of malignant fibrous histiocytoma. This represents an unusual primary bone lesion in the rib. A concise discussion of primary MFH of bone including its radiographic appearance, differential diagnosis, and pathology was presented.

Aged↗
PubMed1995

A pilot study of cyclosporine for the prevention of postsurgical adhesion formation in rats.

OBJECTIVE: Our purpose was to evaluate the efficacy of cyclosporine in preventing primary postsurgical adhesions in the rat model. STUDY DESIGN: Thirty-two Sprague-Dawley rats underwent unilateral uterine horn injury with a combination of unipolar and bipolar cautery. Sixteen of the rats were randomized to the treatment group and received preoperative and daily cyclosporine dosing (10 mg/kg) by gavage for 14 days. At the end of the study all animals were killed, and a standard adhesion scoring system was applied by a blinded examiner. RESULTS: Adhesions were present in 75% of rats in both groups. Treatment did not affect the total adhesion score. CONCLUSION: Cyclosporine does not appear promising as a means to decrease postsurgical adhesion formation.

Animals↗
PubMed1995

Malignant mesothelioma of the tunica vaginalis. A clinicopathologic analysis of 11 cases with review of the literature.

Eleven malignant mesotheliomas of the testicular tunica vaginalis occurred in patients aged 12 to 76 (mean, 54.1) years. Hydrocele, with or without an associated mass, or appreciation of a paratesticular mass accounted for the clinical presentation. One patient had a history of asbestos exposure. Grossly, the tumors typically presented as multiple nodules studding a hydrocele sac, frequently associated with a mass infiltrating the spermatic cord or adjacent testis. Microscopically, five tumors were epithelial and six biphasic, with the typical architectural and cytologic features of mesothelioma. Mixtures of papillary, tubular, and solid patterns predominated in the epithelial areas; interlacing fascicles of spindle cells with scanty stroma characterized the sarcomatous components. All eight of the tumors that were stained for keratin (AE1/AE3) were positive, four of five for epithelial membrane antigen, and four of five for vimentin. Seven of seven tumors were carcinoembryonic antigen negative and five of five B72.3, Leu-M1, and Ber-Ep4 negative. Follow-up ranging from 1 to 15 (mean, 4.3) years was available for seven patients. Three died of disease after 4, 4, and 3 years, and three are alive with disease 2, 2, and 15 years after diagnosis. Two of the latter three patients had extensive local recurrences, one 15 years after the diagnosis of a well-differentiated papillary mesothelioma, the other 2 years following treatment with hydrocelectomy only. One patient who has been followed for only 1 year has no evidence of disease. This series emphasizes a number of important features of testicular mesothelioma; (a) a wide age range with occasional occurrence at a young age, (b) a wide morphologic spectrum with regard to degree of differentiation, and (c) an aggressive natural history with a potential for late recurrence or metastasis of even well-differentiated tumors, suggesting the need for initial aggressive surgical treatment.

Adult↗
PubMed1995

Paratesticular serous papillary carcinoma. A report of six cases.

Six intrascrotal, invasive epithelial neoplasms of serous papillary type arose in the paratesticular region of patients 16 to 42 (mean, 30.8) years of age. Five patients, one with an associated hydrocele, presented with a testicular mass and one with a hydrocele only. The serum CA-125 level was elevated in one of the two patients in whom it was measured. Grossly, the tumors were solid, white, or tan, poorly circumscribed, often gritty masses. Four tumors involved primarily the soft tissue between the testis and epididymis (testiculoepididymal groove) and one, the paratesticular soft tissue. The sixth tumor was confined to the visceral tunica vaginalis at the inferior pole of the testis. The most common microscopic pattern was characterized by invasive, well-formed papillae lined by serous cuboidal or columnar cells with eosinophilic cytoplasm and malignant nuclear features. Psammoma bodies were abundant in all the cases. Areas of borderline serous tumor were present in two tumors and predominated in one. Five of five tumors were positive for keratin (AE1/3), S-100, epithelial membrane antigen, and Ber-EP4; three of five for Leu M1 and B72.3; two of five for carcinoembryonic antigen and placental alkaline phosphatase; and one in five for vimentin. Ultrastructural examination in one case demonstrated gland formation with delicate luminal microvilli and cilia. Follow-up information was available in five cases: Three patients are without evidence of disease after relatively short postoperative intervals of 1, 1, and 3 years, although one of these patients has had a persistently elevated CA-125 level. Two patients had recurrence of their tumors 4 and 7 years after diagnosis, one with diffuse abdominal spread, the other in a cervical lymph node. The latter patient died of his disease 5 years after diagnosis.

Adolescent↗
PubMed1995

Differential metabolism of exogenous platelet-activating factor by glandular epithelial and stromal cells of rabbit endometrium.

Significant changes in platelet-activating factor (PAF; 1-O-alkyl-2-acetyl-sn-glycero-3-phosphorylcholine) concentration have been observed in rabbit endometrium during the preimplantation period, but, under in vitro conditions, constitutive PAF biosynthesis by isolated endometrial tissues was not easily demonstrable. Relative changes in enzymes involved in the synthesis and metabolism of PAF in the tissues may account for this disparity. In addition, during this period of preimplantation, marked changes in PAF receptor concentration have been noted. The present study examines the factors that may modulate the metabolism of exogenous [3H]PAF in the endometrium of rabbits on day 6 of pregnancy. Since preferential [3H]PAF binding in situ by the glandular epithelial, but not by the stromal, cells was demonstrated, their cell-specific metabolism of exogenous [3H]PAF was also examined. After entry into the endometrial cell, [3H]PAF was rapidly metabolized by the sequential action of cytosolic Ca(2+)-independent acetylhydrolase to [3H]lyso-PAF and this was in turn acylated by membrane-associated transacylase to [3H]alkylacyl-glycerylphosphorylcholine. PAF resynthesis was not observed and, in stromal cells, there was a significant build-up of [3H]lyso-PAF, suggesting that lyso-PAF:acetyl-CoA acetyl-transferase may be a limiting factor. In the glandular epithelial cells, however, there was a significant accumulation of a neutral lipid without a significant build-up of [3H]lyso-PAF or [3H]PAF. The neutral lipid co-migrated with the product of phospholipase C-catalysed metabolism of PAF and authentic 1-O-hexadecyl-2-acetyl-glycerol. In addition, the elution times of phospholipase C digestion of C18 PAF and the neutral lipid produced by cellular metabolism of [3H]PAF, determined by gas chromatography/flame ionization detection, were similar. It seems that it is the synthesis of the neutral lipid from reacetylated [3H]lyso-PAF that prevented [3H]PAF accumulation under in vitro conditions. This is the first documentation of the synthesis of this lipid in the mammalian uterus. The lipid may serve as the precursor for de novo PAF synthesis in the glandular epithelial cells during endometrial proliferation.

Acetyltransferases↗
PubMed1995

Changes in diurnal blood pressure variation and red cell and plasma volumes in patients with renal failure who develop erythropoietin-induced hypertension.

Hypertension is the most common side-effect of treatment with recombinant human erythropoietin (EPO) for the anemia of chronic renal failure. To elucidate why this occurs in some patients we measured changes in blood volumes and diurnal blood pressure (BP) variation during treatment. Isotope labelled measurements of red cell and plasma volume (RCV and PV) were carried out along with ambulatory BP monitoring before starting EPO and after target hemoglobin (Hb) was reached. RCV did not differ between the patient group developing EPO-induced hypertension (EpHT, n = 11) and the group with no change in BP (NC, n = 13) either before or after treatment. However PV was significantly lower in the EpHT group after treatment (2.97 vs 3.92 litres; p < 0.025). Mean BPs differed little between groups because antihypertensive medications were increased as necessary for clinical safety but after achieving target Hb, day-night difference in diastolic BP was greater in the EpHT than the NC group (11.5 vs 4.6 mmHg; p < 0.025) due to a greater rise in daytime BP. There were significant correlations between high day-night diastolic BP differences after EPO in all the studied patients and low plasma volumes either pre- or post-EPO. The study group was heterogeneous but the changes were in the same direction irrespective of type of renal replacement therapy. These results suggest that EPO-induced hypertension is associated with increased daytime vasoconstriction and greater hemoconcentration due to lower plasma volume.

Anemia↗
PubMed1994

Primary yolk sac tumors of the mesentery. A report of two cases.

Two yolk sac tumors that arose in the mesentery of the jejunum and the mesentery of the transverse colon of two male patients, aged 2 and 17 years, are reported. Both patients had abdominal masses. The tumors measured 9 and 11 cm in maximum dimension. One of them grew into the bowel lumen. Microscopically, both neoplasms exhibited several of the typical patterns of yolk sac tumor and stained immunohistochemically for alpha-fetoprotein. Both patients received chemotherapy postoperatively and are alive, but follow-up is short. The subject of extragonadal yolk sac tumors is reviewed, and histogenetic implications of their occasional origin in the mesentery is discussed.

Adolescent↗
PubMed1994

Temporal and regional expression of placental lactogen-II messenger ribonucleic acid and protein in the hamster placenta.

The purpose of this investigation was to identify the cell types synthesizing hamster placental lactogen-II (haPL-II) in the chorioallantoic placenta. In addition, temporal changes in haPL-II mRNA expression, in placental mass, and in the proportion of haPL-II-containing cells per unit area were examined. Hamster PL-II mRNA expression was assessed by in situ hybridization and Northern and slot-blot analyses. Cells containing haPL-II protein were identified by immunocytochemical techniques. Placentae were recovered in the morning on Days 6, 8, 10, 12, and 14 of gestation and in the afternoon on Day 15. A single 1-kb haPL-II transcript was first detected on Day 10 of gestation. Hamster PL-II message increased to Day 14 and remained elevated on Day 15. Giant trophoblast cells (GTC) located in the trophospongium were the major source of haPL-II mRNA and protein, although GTC along the periphery of the placenta and in the labyrinth expressed haPL-II as well. Placental weight, trophospongium portion of placental weight, and number of haPL-II-immunostained GTC per unit of placental area increased between Days 12 and 14 and remained elevated to Day 15. These observations indicate that an increased number of haPL-II-producing GTC is a major factor contributing to increased maternal haPL-II serum levels during pregnancy.

Animals↗
PubMed1994

The psi operon of Rhizobium leguminosarum biovar phaseoli: identification of two genes whose products are located at the bacterial cell surface.

We have delineated three short open reading frames, psiA, ORF-P and psiB within the psi operon of Rhizobium leguminosarum biovar phaseoli. psiA, in a multi-copy plasmid, causes inhibition of exopolysaccharide synthesis in R. leguminosarum. In addition, the suppression of exopolysaccharide synthesis due to the multi-copy psiA caused R. leguminosarum strains to stain with the dye calcofluor, a response that does not occur with wild-type strains of this species. Insertions of a defective phoA gene (lacking its promoter, ribosomal binding site and leader sequence) into psiA and psiB were isolated and the precise locations of the insertions were established. PsiA-PhoA and PsiB-PhoA protein fusions were found to express alkaline phosphatase activity indicating that PsiA and PsiB span the inner membrane or are translocated across it.

Alkaline Phosphatase↗